Objective To establish a method for rapid detection of tramadol in urine by liquid-liquid extraction（LLE）-surface-enhanced Raman spectroscopy （SERS）. Methods Tramadol was extracted from urine with chloroform∶isopropyl alcohol （9∶1） extractant and detected in urine samples by enhanced Raman spectroscopy （wavelength 785 nm）. Results The quantitative curve of tramadol was Y=204.35 X−465.62, r=0.9952, and the linear range was 1-100 μg/ml. The detection limit of tramadol by this method （S/N=3） was 0.53 μg/ml. The sensitivity of SERS was higher than that of conventional methods, and it had reasonable reproducibility. Conclusion This method is simple, efficient and economical, and can be used for qualitative and quantitative analysis of tramadol personalized medicine.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

Central memory T (Tcm) cells are a crucial subset in T cell development, playing an important role in long-term immune responses. Tcm cells exhibit strong proliferative capacity, long-term survival characteristics, and re-activation potential, enabling them to rapidly differentiate into effector T cells (Teff) upon antigen re-exposure, thus providing robust immune protection. The function of Tcm cells is regulated by various factors, including antigen exposure, cytokines, and metabolic conditions. A deeper understanding of their metabolic and epigenetic mechanisms under different pathological conditions will contribute to the development of more precise and effective immunotherapeutic strategies. This review elaborates on the origin and characteristics of Tcm cells, as well as their roles in antiviral responses, tumor immunity, and immunotherapy.
Humans ; Memory T Cells/cytology* ; Animals ; Immunologic Memory ; Neoplasms/therapy* ; Immunotherapy

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective To evaluate the myocardial microcirculation function of patients with acute myocardial infarction(AMI)after treatment with myocardial contrast-enhanced ultrasound combined with albumin(ALB)and lipoprotein a[Lp(a)].Methods Ninety-six patients with AMI admitted to our hospital from January 2022 to September 2023 were selected.According to myocardial microcirculation function after treatment,they were divided into a normal function group(56 cases)and a dysfunction group(40 cases).major cardiovascular adverse events were compared between the two groups.major cardiovascular adverse events(MACE),the plateau peak intensity of myocardial contrast ultrasound parameters(A value),the rise rate of microbubble reperfusion(β value),myocardial blood flow(A value×β value),and serum ALB and Lp(a)levels after 48h of treatment were different,so as to determine the evaluation value of myocardial contrast ultrasound,ALB and Lp(a)on myocardial microcirculation function in AMI patients after treatment.Results In the dysfunction group,the parameters A,β,A×β,and serum ALB level,Lp(a)was higher than that in the normal function group(P＜0.05).A,β,A×β,ALB were positively correlated with cardiac function,and Lp(a)was negatively correlated with cardiac function(P＜0.05).CEUS combined with ALB and Lp(a)evaluated the efficacy of myocardial microcirculation in patients with AMI(P＜0.05).The incidence of MACE was higher in the functional group than in the normal functional group(P＜0.05).Conclusion Myocardial contrast-enhanced ultrasound can early evaluate the myocardial microcirculation function in patients with acute myocardial infarction after treatment,and combined with serum ALB and Lp(a),it can improve diagnostic efficacy.

The effect of different concentrations of glycyrrhizic acid (GA) and Zn²⁺ on the self-assembly of metal complexes was investigated by forming metal complexes, and the properties and assembly mechanisms of the formed carrier-free supramolecular hydrogel were characterised. Scanning electron microscopy (SEM) and zeta potential were used to characterise the microscopic morphology and stability of the GA-Zn complex hydrogel, which had spherical-like particles of about 1 μm with good stability; the rheometer was used to detect its materialistic properties, which showed excellent stability, self-healing property and reversibility; through in vitro bacterial inhibition, it was found that the GA-Zn carrier-free supramolecular hydrogel has enhanced bacterial inhibition function after assembly. The hydrogel was also found to possess both anti-inflammatory and antioxidant efficacy when evaluated using LPS and H₂O₂ induced RAW 264.7 cell damage models, respectively. The above results suggest that GA-Zn hydrogel not only has good materialistic properties, but also possesses good antibacterial, anti-inflammatory and antioxidant activities, which has the value of clinical research as a carrier-free multi-functional antimicrobial dressing, and the present study provides a reference for the discovery of novel biomedical materials from active molecules of natural traditional Chinese medicine.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.